119 EXPRESSION PROFILE OF MOLECULAR MARKERS ASSOCIATED WITH EPITHELIAL TO MESENCHYMAL TRANSITION IN RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research1 Apr 2011119 EXPRESSION PROFILE OF MOLECULAR MARKERS ASSOCIATED WITH EPITHELIAL TO MESENCHYMAL TRANSITION IN RENAL CELL CARCINOMA Mototsugu Muramaki, Hideaki Miyake, Tomoaki Terakawa, Yuuji Kusuda, and Masato Fujisawa Mototsugu MuramakiMototsugu Muramaki Kobe, Japan More articles by this author , Hideaki MiyakeHideaki Miyake Kobe, Japan More articles by this author , Tomoaki TerakawaTomoaki Terakawa Kobe, Japan More articles by this author , Yuuji KusudaYuuji Kusuda Kobe, Japan More articles by this author , and Masato FujisawaMasato Fujisawa Kobe, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.185AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES As a feature of aggressive tumors, epithelial to mesenchymal transition (EMT) is characterized by reduced E-cadherin and increased several protein expression including N-cadherin, MMP-2 and MMP-9. This molecular alternation is thought to be contributing to a stroma-oriented cellular adhesion profile with increased tumor cell motility and invasive properties, and it has recently reported in several tumors. However, it is not known whether the EMT phenotype is important for the progress and prognosis of renal cell carcinoma (RCC). The objective of this study was to investigate the association between EMT markers and the progression of RCC after radical nephrectomy. METHODS Expression levels of several EMT markers, including E-cadherin, N-cadherin, MMP-2 and MMP-9, were evaluated by immunohistochemical staining in a consecutive series of 99 patients RCC, consisting of 51 with organ-confined disease and 48 with non-organ-confined disease. All patients including who had metastatic disease at diagnosis underwent radical nephrectomy as a primary treatment. Progression-free survival rates were calculated using the Kaplan-Meier method. Various predictive factors for postoperative recurrence or progression were analyzed using multivariate analysis. RESULTS Median follow-up period was 19.3 months (range 5–101). Among the 48 patients with non-organ-confined disease, 27 patients had metastatic disease at diagnosis. There were significant increase in the incidence of positive expression of N-cadherin, MMP-2 and -9 in non-organ-confined group (p = 0.002, 0.002 and 0.03, respectively). Patients with positive expression of N-cadherin, MMP-2 or MMP-9 had significantly shorter progression-free survival (p < 0.0001, 0.04 and 0.011, respectively). Moreover, presence of metastasis at diagnosis and positive expression of N-cadherin and MMP-9 were shown to be an independent predictor of progression-free survival evaluated by multivariate analysis (p = 0.007, < 0.0001 and < 0.0001, respectively). CONCLUSIONS Among ENT markers investigated in this study, N-cadherin and MMP-9 were significantly associated with worse prognosis in patients with RCC, and they appeared to be independent prognostic factors after radical nephrectomy. These findings suggest that EMT may have an important role for progression of RCC. Patients with high expression levels of N-cadherin and MMP-9 should undergo intensive post-treatment follow-up. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e50 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mototsugu Muramaki Kobe, Japan More articles by this author Hideaki Miyake Kobe, Japan More articles by this author Tomoaki Terakawa Kobe, Japan More articles by this author Yuuji Kusuda Kobe, Japan More articles by this author Masato Fujisawa Kobe, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...